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Preclinical evaluat...
Preclinical evaluation of Affibody molecule for PET imaging of human pancreatic islets derived from stem cells
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- Cheung, Pierre (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Thorngren, Julia (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Zhang, Bo (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Vasylovska, Svitlana (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Lechi, Francesco (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET
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- Persson, Jonas (författare)
- KTH,Proteinvetenskap,Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
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- Ståhl, Stefan, 1961- (författare)
- KTH,Proteinvetenskap,Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
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- Löfblom, John (författare)
- KTH,Proteinvetenskap,Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
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- Korsgren, Olle (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Eriksson, Jonas (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för läkemedelskemi
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- Lau, Joey, 1979- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Eriksson, Olof (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för läkemedelskemi
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(creator_code:org_t)
- Springer Nature, 2023
- 2023
- Engelska.
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 13:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Background: Beta-cell replacement methods such as transplantation of isolated donor islets have been proposed as a curative treatment of type 1 diabetes, but widespread application is challenging due to shortages of donor tissue and the need for continuous immunosuppressive treatments. Stem-cell-derived islets have been suggested as an alternative source of beta cells, but face transplantation protocols optimization difficulties, mainly due to a lack of available methods and markers to directly monitor grafts survival, as well as their localization and function. Molecular imaging techniques and particularly positron emission tomography has been suggested as a tool for monitoring the fate of islets after clinical transplantation. The integral membrane protein DGCR2 has been demonstrated to be a potential pancreatic islet biomarker, with specific expression on insulin-positive human embryonic stem-cell-derived pancreatic progenitor cells. The candidate Affibody molecule ZDGCR2:AM106 was radiolabeled with fluorine-18 using a novel click chemistry-based approach. The resulting positron emission tomography tracer [18F]ZDGCR2:AM106 was evaluated for binding to recombinant human DGCR2 and cryosections of stem-cell-derived islets, as well as in vivo using an immune-deficient mouse model transplanted with stem-cell-derived islets. Biodistribution of the [18F]ZDGCR2:AM106 was also assessed in healthy rats and pigs. Results: [18F]ZDGCR2:AM106 was successfully synthesized with high radiochemical purity and yield via a pretargeting approach. [18F]ZDGCR2:AM106 retained binding to recombinant human DCGR2 as well as to cryosectioned stem-cell-derived islets, but in vivo binding to native pancreatic tissue in both rat and pig was low. However, in vivo uptake of [18F]ZDGCR2:AM106 in stem-cell-derived islets transplanted in the immunodeficient mice was observed, albeit only within the early imaging frames after injection of the radiotracer. Conclusion: Targeting of DGCR2 is a promising approach for in vivo detection of stem-cell-derived islets grafts by molecular imaging. The synthesis of [18F]ZDGCR2:AM106 was successfully performed via a pretargeting method to label a site-specific covalently bonded fluorine-18 to the Affibody molecule. However, the rapid washout of [18F]ZDGCR2:AM106 from the stem-cell-derived islets graft indicates that dissociation kinetics can be improved. Further studies using alternative binders of similar classes with improved binding potential are warranted.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Affibody molecule
- DGCR2
- Diabetes
- Fluorine-18 chemistry
- PET
- Stem cells
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Cheung, Pierre
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Thorngren, Julia
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Zhang, Bo
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Vasylovska, Svit ...
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Lechi, Francesco
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Persson, Jonas
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visa fler...
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Ståhl, Stefan, 1 ...
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Löfblom, John
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Korsgren, Olle
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Eriksson, Jonas
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Lau, Joey, 1979-
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Eriksson, Olof
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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EJNMMI Research
- Av lärosätet
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Kungliga Tekniska Högskolan
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Uppsala universitet